Animal Core

动物核心

• 批准号: 7218288
• 负责人: WILLIAM H WELCH
• 金额: $ 32.75万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7218288
• 关键词: Adult; Aftercare; Anesthesia procedures; Angiotensin II; Animals; Antioxidants; Binding Proteins; Blood Pressure; Blood flow; Blood gas; Breeding; Cardiovascular system; Conscious; Control Groups; Cuprozinc Superoxide Dismutase; Data; Data Analyses; Dopamine; Dopamine Receptor; Endothelin; Enzymes; Fibroblast Growth Factor; Filtration; Genetically Engineered Mouse; Glomerular Filtration Rate; Heart Rate; Hormones; Infusion procedures; Kidney; Knock-out; Knockout Mice; Manganese Superoxide Dismutase; Measures; Mus; NADPH Oxidase; Oxidative Stress; Oxygen Consumption; Oxygen measurement, partial pressure, arterial; Physiological; Physiology; Plasma; Program Research Project Grants; Protein Overexpression; Reactive Oxygen Species; Renal Blood Flow; Renal function; Renin; Research Personnel; Series; Small Interfering RNA; Superoxide Dismutase; Testing; Transgenic Mice; Transgenic Organisms; Ultrasonics; Urine; Vascular resistance; Week; animal colony; cohort; extracellular; human CYBA protein; human FGF3 protein; kidney vascular structure; knock-down; male; mouse model; programs; receptor; research study

Genetically engineered mice required to study oxidative stress in this Program Project Grant will be bred and maintained by Core B. Oxidative stress is due to excess reactive oxygen species generated by NADPH oxidase (NOX) or reduced function of superoxide dismutases (SOD), the major antioxidant defense. The Core will maintain two current strains of C57/BI6 background knockout mice: the extracellular superoxide dismutase (EC-SOD) knockout and the dopamine, type 5 receptor (D5R). In addition, two colonies of knockout mice will be developed: intracellular superoxide dismutase (IC-SOD) knockout mice and mice heterozygous for manganese superoxide dismutase (Mn-SOD). The Mn-SOD knockout is lethal. Core B will use heterozygous breeders to produce both wild type and knockouts in a single litter. Adult male knockout mice will be used for all experiments and the control group will be adult male wild type littermates. In addition, Core B will measure conscious mean arterial blood pressure, by radiotelemetry and renal blood flow, by ultrasonic flow probes in all mouse models used in the Program. This will include additional mice treated with small interfering RNA to knock down p22phox, the critical subunit for NOX and for fibroblast growth factor transgenic mice. Function in these mice will be measured after treatment with vehicle or angiotensin II to induce oxidative stress. Additional mice in each group will be used to measure renal function, including glomerular filtration rate, renal plasma and blood flow, renal vascular resistance, urine flow, oxygen consumption and blood gas levels under anesthesia. Core B will also measure a series of hormones, enzymes and end products that are related to oxidative stress effects in the kidney. Core B will also provide technical assistance to each project on animal issues, including mouse physiology and data analysis.

本项目资助将培育研究氧化应激所需的基因工程小鼠 并由核心 B 维持。氧化应激是由于核心 B 产生的过量活性氧造成的。 NADPH 氧化酶 (NOX) 或主要抗氧化剂超氧化物歧化酶 (SOD) 功能降低 防御。 Core 将保留两种当前的 C57/BI6 背景基因敲除小鼠品系： 细胞外超氧化物歧化酶 (EC-SOD) 敲除和多巴胺 5 型受体 (D5R)。在 此外，还将开发两个基因敲除小鼠群体：细胞内超氧化物歧化酶（IC-SOD） 敲除小鼠和锰超氧化物歧化酶（Mn-SOD）杂合小鼠。锰SOD 淘汰赛是致命的。核心B将使用杂合育种者在a中生产野生型和敲除型 单窝。所有实验均使用成年雄性敲除小鼠，对照组为成年小鼠 雄性野生型同窝仔。此外，Core B 将通过以下方式测量有意识的平均动脉血压： 通过超声波流量探头在该计划中使用的所有小鼠模型中进行无线电遥测和肾血流量。 这将包括用小干扰 RNA 治疗的其他小鼠，以敲低 p22phox，这是关键的 NOX 亚基和成纤维细胞生长因子转基因小鼠。将测量这些小鼠的功能 用载体或血管紧张素 II 治疗后诱导氧化应激。每组中额外的小鼠将 用于测量肾功能，包括肾小球滤过率、肾血浆和血流量、肾功能 麻醉下的血管阻力、尿流量、耗氧量和血气水平。核心B将 还测量一系列与氧化应激效应相关的激素、酶和最终产物 在肾脏。核心B还将为每个有关动物问题的项目提供技术援助，包括 小鼠生理学和数据分析。